Effects of dexmedetomidine and propofol on lower esophageal sphincter and gastroesophageal pressure gradient in healthy volunteers.

BACKGROUND: Many anesthetics reduce lower esophageal sphincter pressure (LESP). Reduced pressure and consequent reduction in the gastroesophageal pressure gradient (GEPG) thus promotes gastroesophageal reflux and may contribute to aspiration pneumonia and associated morbidity. Therefore, the authors compared LESP and GEPG during dexmedetomidine and propofol sedation. METHODS: Using a randomized, double-blind, crossover design, 11 healthy volunteers were sedated on 2 separate days. Baseline LESP and GEPG were recorded each day. Subsequently, on each day volunteers received three 40-min-long sedative infusions of increasing doses of 0.6, 1.2, and 2.4 ng/ml dexmedetomidine or 1, 2, and 4 microg/ml propofol. LESP and GEPG were recorded during inhalation and expiration at 20 and 40 min after starting each infusion phase, and these measurements were averaged. Results are presented as mean (95% confidence interval). RESULTS: Two subjects did not return for the dexmedetomidine study day, and the dexmedetomidine results were unusable in another; propofol results in these volunteers were nonetheless retained for analysis. There were no significant differences in LESP and GEPG as a function of drug. However, there was a small but significant 7.4 (-1.6 to -13.2) mmHg (approximately 25%) dose-dependent decrease in LESP over the range of targeted low to high blood levels of each drug. CONCLUSIONS: Both dexmedetomidine and propofol have similar effects on LESP and GEPG. Although both of the drugs cause some decrease in LESP at high concentrations, it is unlikely that this effect would promote gastroesophageal reflux during sedation.

Early postoperative subcutaneous tissue oxygen predicts surgical site infection.

BACKGROUND: Subcutaneous oxygen partial pressure is one of several determinants of surgical site infections (SSIs). However, tissue partial pressure is difficult to measure and requires invasive techniques. We tested the hypothesis that early postoperative tissue oxygen saturation (Sto(2)) measured with near-infrared spectroscopy predicts SSI. METHODS: We evaluated Sto(2) in 116 patients undergoing elective colon resection. Saturation was measured near the surgical incision, at the upper arm, and at the thenar muscle with an InSpectra™ tissue spectrometer model 650 (Hutchinson Technology Inc., Hutchinson, MN) 75 minutes after the end of surgery and on the first postoperative day. An investigator blinded to Sto(2) assessed patients daily for wound infection. Receiver operating characteristic curves were used to analyze the performance of Sto(2) measurements as a predictor of SSI. RESULTS: In 23 patients (≈ 20%), SSI was diagnosed 9 ± 5 days (mean ± SD) after surgery. Patients who did and did not develop an SSI had similar age (48 ± 14 vs 48 ± 15 years, respectively; P = 0.97) and gender (female:male, 15:8 vs 46:47, respectively), but patients who developed SSI weighed more (body mass index 32 ± 7 vs 27 ± 6 kg/m(2); P < 0.01). Sto(2) at the upper arm was lower in patients who developed SSI than in those who did not develop SSI (52 ± 22 vs 66 ± 21; P = 0.033), and these measurements had a sensitivity of 71% and specificity of 60% for predicting SSI, using Sto(2) of 66% as the cutoff point. CONCLUSION: Sto(2) measured at the upper arm only 75 minutes after colorectal surgery predicted development of postoperative SSI, although the infections were typically diagnosed more than a week later. Although further testing is required, Sto(2) measurements may be able to predict SSI and thus allow earlier preventive measures to be implemented.

The effect of aminophylline on loss of consciousness, bispectral index, propofol requirement, and minimum alveolar concentration of desflurane in volunteers.

BACKGROUND: Adenosine is a soporific neuromodulator; aminophylline, which is clinically used as a bronchodilator, antagonizes the action of adenosine in the central nervous system. Thus, we tested the hypothesis that aminophylline delays loss of consciousness (LOC) and speeds recovery of consciousness (ROC) with propofol anesthesia, and that aminophylline increases the minimum alveolar concentration (MAC) of desflurane. METHODS: In this double-blind crossover study, volunteers were randomized to either aminophylline or saline on different days. Aminophylline 6 mg/kg was given IV, followed by 1.5 mg x kg(-1) x h(-1) throughout the study day. After 1 h of aminophylline or saline administration, propofol 200 mg was given at a rate of 20 mg/min. The bispectral index was continuously monitored, as were times to LOC and ROC. After recovery from propofol, general anesthesia was induced with sevoflurane and subsequently maintained with desflurane. The Dixon "up-and-down" method was used to determine MAC in each volunteer after repeated tetanic electrical stimulation. RESULTS: Eight volunteers completed both study days. Time to LOC was prolonged by aminophylline compared with saline (mean +/- SD) (7.7 +/- 2.03 min vs 5.1 +/- 0.75 s, respectively, P = 0.011). The total propofol dose at LOC was larger with aminophylline (2.2 +/- 0.9 vs 1.4 +/- 0.4 mg/kg, P = 0.01), and the time to ROC was shorter (6.18 +/- 3.96 vs 12.2 +/- 4.73 min, P = 0.035). The minimum bispectral index was greater with aminophylline (51 +/- 15 vs 38 +/- 9, P = 0.034). There was no difference in MAC. CONCLUSION: Aminophylline decreases the sedative effects of propofol but does not affect MAC of desflurane as determined by tetanic electrical stimulation.

Suppression of shivering during hypothermia using a novel drug combination in healthy volunteers.

BACKGROUND: Hypothermia may be beneficial in stroke victims; however, it provokes vigorous shivering. Buspirone and dexmedetomidine each linearly reduce the shivering threshold with minimal sedation and no respiratory depression. This study tested the hypotheses that the combination of buspirone and dexmedetomidine would (1) synergistically reduce the shivering threshold, (2) synergistically reduce the gain and maximum intensity of shivering, and (3) produce sufficient inhibition to permit cooling to 34 degrees C without excessive hypotension or sedation. METHODS: Eight healthy men were randomly assigned on 4 days to (1) no drug, (2) buspirone (60 mg orally), (3) dexmedetomidine (intravenous infusion to target plasma concentration of 0.6 ng/ml), or (4) combination of buspirone and dexmedetomidine at same doses. Lactated Ringer's solution (approximately 3 degrees C) was infused intravenously to decrease tympanic membrane temperature by 1.5 degrees C/h. Shivering threshold was defined as an increase in oxygen consumption greater than 20%. Sedation was evaluated using the Observer's Assessment of Sedation/Alertness scale. RESULTS: Mean arterial pressure and heart rate were slightly lower on dexmedetomidine and combination days. Likewise, the level of sedation was statistically different on these 2 days but clinically unimportant. Buspirone reduced the shivering threshold from 36.6 degrees C +/- 0.4 degrees C to 35.9 degrees C +/- 0.4 degrees C, dexmedetomidine reduced it to 34.7 degrees C +/- 0.5 degrees C, and the combination to 34.1 +/- 0.4 degrees C. The interaction effect of 0.04 degrees C was not significant. The gain of shivering and maximum shivering intensity were similar on each day. CONCLUSIONS: The combination of buspirone and dexmedetomidine additively reduced the shivering threshold. Thus, supplementing dexmedetomidine with buspirone blocks shivering and causes only minimal sedation.

The correlation between bispectral index and observational sedation scale in volunteers sedated with dexmedetomidine and propofol.

BACKGROUND: Bispectral index (BIS) is a widely used quantitative parameter for evaluating anesthesia and sedation levels. Dexmedetomidine is a novel sedative, providing sedation while patients remain cooperative and can be easily aroused; as a consequence, BIS used with dexmedetomidine may poorly characterize sedation. Thus, we tested the hypothesis that BIS values are lower with dexmedetomidine than with propofol at comparable Observer's Assessment of Alertness and Sedation (OAA/S) scores. METHODS: This was a randomized, 2-day, crossover study. On the first study day, healthy volunteers were randomly allocated to either propofol or dexmedetomidine sedation. Drugs were administered using computer-controlled infusions targeting an effect-site concentration of 1, 2, and 4 microg/mL for propofol or a plasma concentration of 0.6, 1.2, and 2.4 ng/mL for dexmedetomidine. The relationship between BIS and OAA/S score was obtained 20 and 40 min after changing each drug concentration. BIS values at each OAA/S score were compared between drugs. The cutoff values of BIS for OAA/S score of < or =2 were obtained by analysis of receiver operating characteristic curves. RESULTS: Nine volunteers were included in our analysis. Heart rates decreased significantly with dexmedetomidine sedation. ETco(2) was significantly increased with high doses of propofol but did not increase with high doses of dexmedetomidine. BIS values at OAA/S scores of 1, 2, 3, 4, and 5 during propofol sedation were 95.5 (90-97), 78 (71-84.5), 67 (64-70), 57 (51.5-60), and 34 (30-37), respectively. BIS values at OAA/S scores of 1, 2, 3, 4, and 5 during dexmedetomidine sedation were 95 (79-98), 62 (53.5-68.5), 45.5 (45.3-52), 39.5 (34.3-41.8), and 24.5 (22.5-30.5), respectively. BIS values were significantly less with dexmedetomidine than propofol at OAA/S responsiveness scores of 2, 3, and 4. The calculated cutoff BIS values for OAA/S scores of < or =2 were 67 (sensitivity of 86%, specificity of 97%, and area under the curve of 0.98) for propofol and 46 (sensitivity of 84%, specificity of 91%, and area under the curve of 0.96) for dexmedetomidine. CONCLUSION: The combination of both BIS and sedative scales could provide different and complementary data to the clinician evaluating the patient's response to sedation than would either tool alone, especially when dexmedetomidine is used.